Denileukin diftitox, recombinant, Ontak, is an example of a drug that acts like a Trojan horse. One part of the molecule is involved in recognition and binds selectively with the diseased cell, and a highly toxic second part of the molecule effects a kill. Denileukin diftitox is a fusion protein expressed by a recombinant strain of E. coli. It is an rDNA-derived cytotoxic protein composed of the amino acid sequences for diphtheria toxin fragments A and B (Meti-Thr387)-His, followed by the sequences for IL-2 (Ala1-Thr133). The fusion protein has a molecular mass of 58,000 Da. We can think of this large protein as a molecule of diphtheria toxin in which the receptor-binding domain has been replaced by IL-2 sequences, thereby changing its binding specificity. Cells that express the high-affinity (a, ¡, y) IL-2 receptor bind the protein tightly. The IL-2 component is used as a director to bring the cytotoxic species in contact with tumor cells. The diphtheria toxin inhibits cellular protein synthesis and the cells die. Malignant cells in certain leukemias and lymphomas, including cutaneous T-cell lymphoma, express the high-affinity IL-2 receptor on their cell surfaces. It is these cells that denileukin diftitox targets.
Denileukin diftitox is indicated for the treatment of persistent or recurrent cutaneous T-cell lymphoma whose malignant cells express the CD25 component of the IL-2 receptor.
Denileukin diftitox is supplied as a frozen solution in water for injection. It should be stored at — 10°C or colder. It is suggested that the vials be thawed in a refrigerator at 2°C to 8°C for less than 24 hours or at room temperature for 1 to 2 hours. Prepared solutions should be used within 6 hours. The drug is administered by IV infusion from a bag or through a syringe pump.
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